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Philadelphia Chromosome Positive Acute Lymphoblastic LeukemiaPhase 2GMALL-EVOLVENCT06061094

Randomized Trial in Adult de Novo Ph Positive ALL With Chemotherapy, Imatinib or Ponatinib, Blinatumomab and SCT

A Phase 2 study testing Imatinib, Ponatinib and Blinatumomab in people with Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia, run by Goethe University at 85 sites in Germany.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial summary

The current Standard of Care (SoC) in younger patients with Ph+ ALL is Imatinib in combination with low-dose chemotherapy, change of TKI in case of persistent MRD above 10-3 after consolidation I and indication for stem cell transplantation. Read more about this study

Who is it for?
Ages 18 to 65 years
What is being tested?
Imatinib, Ponatinib and Blinatumomab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
220 participants
Where
85 sitesGermany
Study dates
14 Jul 2023to 1 Jul 2029
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Male or female patients >= 18 years, <=65 years
  • Philadelphia chromosome or BCR-ABL1 positive ALL
  • Not previously treated except with corticosteroids ≤ 7 days, standard GMALL prephase with dexamethasone and cyclophosphamide including intrathecal therapy, hydroxyurea, a single dose vincristine or other cytostatic drugs and start of standard induction for Ph-positive ALL (1 dose vincristine, 1 dose of Rituximab, 2 doses dexamethasone and up to 5 days Imatinib)
  • ECOG performance status ≤2
  • Signed written inform consent
  • Molecular evaluation for BCR-ABL1 performed
Show all 13Show fewer
  • Negative pregnancy test in women of childbearing potential
  • Woman of childbearing potential willing to use 2 highly effective methods of contraception while receiving study treatment and for an additional 3 months after the last dose of study treatment (Pearl-Index <1%). Male who has a female partner of childbearing potential willing to use 2 highly effective forms of contraception while receiving study treatment and for at least an additional 3 months after the last dose of study treatment (Pearl-Index <1%).
  • Normal serum levels > LLN (lower limit of normal) of potassium and magnesium, or corrected to within normal limits with supplements, prior to the first dose of study medication
  • Serum lipase ≤ 1.5 x ULN. For serum lipase > ULN - ≤ 1.5 x ULN, value must be considered not clinically significant and not associated with risk factors for acute pancreatitis
  • Normal QTcF interval ≤450 ms for males and ≤470 ms for females
  • Signed and dated written informed consent is available
  • Participation in the registry of the German Multicenter Study Group for Adult ALL (GMALL)

Who cannot join

  • History of malignancy other than ALL diagnosed within 5 years (yrs) prior to start of protocol-specified therapy with defined exceptions
  • Contraindications against the use of Imatinib, Ponatinib, chemotherapy or Blinatumomab
  • Patient previously treated with tyrosine kinase inhibitors
  • Nursing women
  • Known impaired cardiac function, including any of the following: as detailed in protocol
  • Symptomatic peripheral vascular disease
Show all 18Show fewer
  • Any history of ischemic stroke or transient ischemic attacks (TIAs)
  • Uncontrolled hypertriglyceridaemia
  • History or presence of clinically relevant CNS pathology as detailed in protocol
  • History or active relevant autoimmune disease
  • Known hypersensitivity to immunoglobulins or to any other component of the study drug formulation
  • Known diagnosis of human immunodeficiency virus (HIV) infection (HIV testing is not mandatory) or active infection with Hepatitis B or C
  • History of pancreatitis within 6 months previous to start of treatment within the trial
  • Treatment with any other investigational agent or participating in another trial within 30 days prior to entering this study
  • Inadequate hepatic functions defined as ASAT or ALAT > 2,5 times the institutional upper limit of normal or > 5 times ULN if considered due to leukemia
  • Total bilirubin > 1.5-fold the institutional upper limit unless considered to be due to organ involvement by the leukemia or to M. Gilbert / M. Meulengracht
  • Concurrent severe diseases which exclude the administration of therapy e.g. severe, uncontrolled acute or chronic infections
  • Inability to understand and/or unwillingness to sign a written informed consent

Trial locations and contacts

85 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Nicola Goekbuget, MD contact

0049-6963016365

goekbuget@em.uni-frankfurt.de

Fabian Lang, MD contact

0049-69630183044

f.lang@med.uni-frankfurt.de

85 sites in 1 country

Germany85 sites, 85 recruiting

  • Uniklinik RWTH Aachen

    Aachen, 52074

    Recruiting

  • Klinikum Aschaffenburg

    Aschaffenburg, 63739

    Recruiting

  • Klinikum Augsburg

    Augsburg, 86156

    Recruiting

  • Helios Klinikum Bad Saarow

    Bad Saarow, 15526

    Recruiting

  • Klinikum Bayreuth

    Bayreuth, 95445

    Recruiting

  • Vivantes Klinikum am Urban

    Berlin, 10967

    Recruiting

  • Charité Universitätsmedizin Berlin

    Berlin, 12220

    Recruiting

  • Vivantes Klinikum Neukölln

    Berlin, 12351

    Recruiting

  • Helios Klinikum Berlin-Buch

    Berlin, 13125

    Recruiting

  • Charite Berlin Virchow Klinikum

    Berlin, 13353

    Recruiting

  • Evangelisches Krankenhaus Bielefeld

    Bielefeld, 33611

    Recruiting

  • UK Knappschaftskrankenhaus Bochum

    Bochum, 44892

    Recruiting

  • Evangelische Kliniken Bonn

    Bonn, 53113

    Recruiting

  • Universitätsklinikum Bonn

    Bonn, 53127

    Recruiting

  • Städtisches Klinikum Braunschweig

    Braunschweig, 38114

    Recruiting

  • Klinikum Bremen-Mitte

    Bremen, 28205

    Recruiting

  • Klinikum Chemnitz

    Chemnitz, 09116

    Recruiting

  • Universitätsklinikum Köln

    Cologne, 50937

    Recruiting

  • Klinikum Darmstadt

    Darmstadt, 64283

    Recruiting

  • Städtisches Klinikum Dessau

    Dessau, 06847

    Recruiting

  • Klinikum Dortmund

    Dortmund, 44137

    Recruiting

  • St. Johannes Hospital Dortmund

    Dortmund, 44137

    Recruiting

  • Universitätsklinikum Carl Gustav Carus Dresden

    Dresden, 01307

    Recruiting

  • Helios Klinikum Duisburg

    Duisburg, 47166

    Recruiting

  • Universitätsklinikum Düsseldorf

    Düsseldorf, 40225

    Recruiting

  • Marien Hospital Düsseldorf

    Düsseldorf, 40479

    Recruiting

  • Universitätsklinikum Erlangen

    Erlangen, 91054

    Recruiting

  • St.-Antonius-Hospital

    Eschweiler, 52249

    Recruiting

  • Universitätsklinikum Essen

    Essen, 45147

    Recruiting

  • Evangelisches Krankenhaus Essen-Werden

    Essen, 45239

    Recruiting

  • Department of Medicine, Hematology and Oncology, Goethe University Hospital Frankfurt

    Frankfurt, 60580

    Nicola Goekbuget, MD, 0049-6963016365, goekbuget@em.uni-frankfurt.de

    Fabian Lang, MD, 0049-69630183044, fabian.lang@kgu.de

    Recruiting

  • Universitätsklinikum Freiburg

    Freiburg im Breisgau, 79106

    Recruiting

  • Niels-Stensen-Kliniken Georgsmarienhütte

    Georgsmarienhütte, 49124

    Recruiting

  • Wilhelm-Anton-Hospital

    Goch, 47574

    Recruiting

  • Universitätsmedizin Göttingen

    Göttingen, 37075

    Recruiting

  • Universitätsmedizin Greifswald

    Greifswald, 17475

    Recruiting

  • Klinikum Gütersloh

    Gütersloh, 33332

    Recruiting

  • Katholisches Krankenhaus Hagen

    Hagen, 58097

    Recruiting

  • Universitätsklinikum Halle

    Halle, 06120

    Recruiting

  • Asklepios Klinik St. Georg Hamburg

    Hamburg, 20099

    Not yet recruiting

  • Universitätsklinikum Hamburg-Eppendorf

    Hamburg, 20251

    Recruiting

  • Medizinische Hochschule Hannover

    Hanover, 30625

    Recruiting

  • Universitätsklinikum Heidelberg

    Heidelberg, 69120

    Recruiting

  • Marien Hospital Herne

    Herne, 44625

    Recruiting

  • Universitätsklinikum des Saarlandes

    Homburg, 66421

    Recruiting

  • Klinikum Idar-Oberstein

    Idar-Oberstein, 55743

    Recruiting

  • Universitätsklinikum Jena

    Jena, 07747

    Recruiting

  • Städtisches Klinikum Karlsruhe

    Karlsruhe, 76133

    Recruiting

  • St. Vincentius-Kliniken Karlsruhe

    Karlsruhe, 76137

    Recruiting

  • Klinikum Kassel

    Kassel, 34125

    Recruiting

  • Universitätsklinikum Kiel

    Kiel, 24105

    Recruiting

  • Gemeinschaftsklinikum Mittelrhein

    Koblenz, 56068

    Recruiting

  • Universitätsklinikum Leipzig

    Leipzig, 04103

    Recruiting

  • Märkische Kliniken Lüdenscheid

    Lüdenscheid, 58515

    Recruiting

  • Universitätsklinikum Magdeburg

    Magdeburg, 39120

    Recruiting

  • UNIVERSITÄTSMEDIZIN der Johannes Gutenberg-Universität Mainz

    Mainz, 55131

    Not yet recruiting

  • Universitätsklinikum Mannheim

    Mannheim, 68167

    Recruiting

  • Philipps-Universität Marburg

    Marburg, 35043

    Recruiting

  • Kliniken Maria Hilf Möchengladbach

    Möchengladbach, 41063

    Recruiting

  • LMU Klinikum München

    München, 81377

    Recruiting

  • Klinikum Rechts der Isar TU München

    München, 81675

    Recruiting

  • Universitätsklinikum Münster

    Münster, 48149

    Recruiting

  • Klinikum Nürnberg

    Nuremberg, 90419

    Recruiting

  • Ortenau Klinikum Offenburg

    Offenburg, 77654

    Recruiting

  • Klinikum Oldenburg

    Oldenburg, 26133

    Recruiting

  • Brüderkrankenhaus St. Josef Paderborn

    Paderborn, 33098

    Recruiting

  • Klinikum Passau

    Passau, 94032

    Recruiting

  • Klinikum Ernst von Bergmann

    Potsdam, 14467

    Not yet recruiting

  • Krankenhaus Barmherzige Brüder Regensburg

    Regensburg, 93049

    Recruiting

  • Universitätsklinikum Regensburg

    Regensburg, 93053

    Recruiting

  • Universitätsklinikum Rostock

    Rostock, 18057

    Recruiting

  • Agaplesion Diakonieklinikum Rotenburg

    Rotenburg (Wümme), 27342

    Recruiting

  • Diakonie-Krankenhaus Schwäbisch-Hall

    Schwäbisch Hall, 74523

    Recruiting

  • Katharinenhospital Stuttgart

    Stuttgart, 70174

    Recruiting

  • Diakonissenkrankenhaus Stuttgart

    Stuttgart, 70176

    Recruiting

  • Robert-Bosch-Krankenhaus Stuttgart

    Stuttgart, 70376

    Recruiting

  • Klinikum Traunstein

    Traunstein, 83278

    Recruiting

  • Mutterhaus der Borromäerinnen Trier

    Trier, 54290

    Recruiting

  • Krankenhaus d. Barmherzigen Brüder

    Trier, 54292

    Not yet recruiting

  • Universitätsklinikum Tübingen

    Tübingen, 72076

    Recruiting

  • Universitätsklinikum Ulm

    Ulm, 89081

    Recruiting

  • Klinikum Schwarzwald-Baar

    Villingen-Schwenningen, 78052

    Recruiting

  • Helios Klinikum Wuppertal

    Wuppertal, 42283

    Recruiting

  • Universitätsklinikum Würzburg

    Würzburg, 97080

    Recruiting

  • Heinrich-Braun Klinikum

    Zwickau, 08060

    Recruiting

Other trials in Germany

About this study

Official title: A Multicentre, Randomized Trial in Adults With de Novo Philadelphia-Chromosome Positive Acute Lymphoblastic Leukemia to Assess the Efficacy of Ponatinib Versus Imatinib in Combination With Low-intensity Chemotherapy, to Compare End of Therapy With Indication for SCT Versus TKI, Blinatumomab and Chemotherapy in Optimal Responders and to Evaluate Blinatumomab in Suboptimal Responders (GMALL-EVOLVE)

The current Standard of Care (SoC) in younger patients with Ph+ ALL is Imatinib in combination with low-dose chemotherapy, change of TKI in case of persistent MRD above 10-3 after consolidation I and indication for stem cell transplantation.

The EVOLVE trial aims to answer three questions challenging the current SoC:

Read more

Use of Ponatinib compared to Imatinib both in combination with low-dose chemotherapy and consolidation I (randomization I).

In MRD good responders: Omit end of therapy in primary care and indication for SCT but continue therapy with TKI, chemotherapy and Blinatumomab as additional antileukemic compound (randomization II).

In MRD poor responders: Omit indication for TKI change but give instead Blinatumomab followed by end of therapy in primary care and indication for SCT (non-randomized).

Being tested
Imatinib, Ponatinib, Blinatumomab, Indication for stem cell transplantation
Keywords
Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia, Tyrosinekinase Inhibitors, Blinatumomab

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ImatinibDrug

    Imatinib 600mg QD plus Chemotherapy

  • PonatinibDrug

    Ponatinib 45 mg QD plus chemotherapy

  • BlinatumomabDrug

    Patients with molecular failure or intermediate response receive one cycle Blinatumomab before SCT; Patients with molecular CR randomized to the experimental arm receive 3 cycles Blinatumomab + chemotherapy

  • Indication for stem cell transplantationOther

    Patients with molecular CR randomized to the standard arm have an indication for SCT; patients with molecular failure or intermediate response have an indication for SCT. SCT is not part of the trial.

Study groups in NCT06061094
Study groupRoleWhat they receive
A: Imatinib + low dose chemotherapyActive comparatorImatinib 600mg QD + low dose chemotherapy induction and consolidation I (Standard Arm of Randomization I)
Receives: Drug: Imatinib
B: Ponatinib + low dose chemotherapyExperimentalPonatinib 45mg QD (reduction to 30mg QD after Induction) + low dose chemotherapy induction and consolidation I (Experimental Arm of Randomization I)
Receives: Drug: Ponatinib
C: Molecular CR: End of therapy with indication for SCTActive comparatorMolecular CR: End of therapy with indication for SCT (Standard Arm of Randomization II)
Receives: Other: Indication for stem cell transplantation
D: Molecular CR: continuation with Imatinib/Ponatinib (per Rando I), chemotherapy and BlinatumomabExperimentalMolecular CR: No end of therapy with indication for SCT but and continuation with Imatinib/Ponatinib (per Randomization I), chemotherapy and Blinatumomab (Experimental Arm of Randomization II)
Receives: Drug: Imatinib; Drug: Ponatinib; Drug: Blinatumomab
E: Mol Fail / Mol NE: Continuation with Imatinib/Ponatinib (per Rando I) and addition of BlinaExperimentalMolecular Failure / Molecular Not Evaluable: Continuation with Imatinib/Ponatinib (per Randomization I) and addition of Blinatumomab (Experimental Arm)
Receives: Drug: Imatinib; Drug: Ponatinib; Drug: Blinatumomab; Other: Indication for stem cell transplantation

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. OS in MolCR patients treated with TKI-Chemo-Blina versus (vs) EOT with indication for SCT (Standard of Care)

    Probability of overall survival up to 4 years from randomization I in patients with mo-lecular remission after consolidation 1 comparing a combination treatment of TKI, Blina-tumomab and chemotherapy versus EOT with indication for SCT

    Measured: up to 4 years from randomization I

Secondary outcomes (1)

  1. Rate of molecular complete remission at week 11 after consolidation

    Rate of molecular complete remission at week 11 after consolidation with chemotherapy in combination with Ponatinb versus Imatinib

    Measured: week 11 after consolidation

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted29 Sep 2023
  2. Study start14 Jul 2023
  3. Primary completion1 Jul 2029 (estimated)
  4. Study completion1 Jul 2029 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
220 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06061094
Sponsor's protocol ID
GMALL-EVOLVE
Other IDs
2022-000760-21
Acronym
GMALL-EVOLVE
Status last verified
Sep 2024
First submitted
20 Aug 2023
Last updated
29 Apr 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Davis KL, Yao CC, Zimmerman JAO, Rau RE. Immunotherapy in B-Cell Acute Lymphoblastic Leukemia. J Natl Compr Canc Netw. 2025 Dec;23(12):e257067. doi: 10.6004/jnccn.2025.7067.

    PubMed 41671463

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Imatinib, Ponatinib and Blinatumomab in people with Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia, run by Goethe University at 85 sites in Germany.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 13 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 29 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 85 sites in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Nicola Goekbuget, MD (0049-6963016365, goekbuget@em.uni-frankfurt.de), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

OS in MolCR patients treated with TKI-Chemo-Blina versus (vs) EOT with indication for SCT (Standard of Care) (time frame: up to 4 years from randomization I). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06061094, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Apr 2025.

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